Forschungsprojekte (Drittmittel)

VISTRIE

Viral Strategies of Immune Evasion

VISTRIE HomeThe Helmholtz Virtual Institute VISTRIE (Viral Strategies of Immune Evasion) comprises seven partners from German Universities and Research, as well as the Rijeka School of Medicine from Croatia. The focus of the Institute is on the study of the immune system by means of viral genetics.

Viruses are parasites that are most intimately associated with their hosts, because their replication is intracellular by definition. To survive, they had to adapt to our immune system through millions of years of natural selection and co-evolution. Their fast replication allows them to evolve thousands of times faster than their hosts and gives them a chance to always remain one step ahead in the competition with the host immune system, producing viral strategies of immune evasion.

It follows that viral immune evasive genes (evasins) are selected to target the most efficient antiviral mechanisms, because natural selection rewards the viruses who suppress the relevant and efficient immune mechanisms. Moreover, it follows that viruses that coevolved with one distinct host species had the best chance to adapt themselves to the species-specific immune mechanisms of a given host. 

Mission

The mission of VISTRIE is to harness millions of years of directed virus evolution and use it to focus on the immunological mechanisms that the viruses have identified as the most important in their control.

Research Objectives

The VISTRIE members share a common experimental platform by focusing on the immune evasion mechanisms of cytomegaloviruses, a family of viruses that coevolve with virtually all mammalian species, from mice to men. The human cytomegalovirus (HCMV) has the largest genome among viruses know to infect humans, whereas the mouse cytomegalovirus (MCMV) carries numerous homologies to HCMV, and allows the experimental study of evasins in biological systems. Therefore, the joint effort of the institute members allows them to translate the knowledge acquired in experimental animal systems to the conditions that are clinically relevant.

The VISTRIE partners work on three research topics, which are then further separated in several work-packages. The structure of the topics and work packages is:

Interferons (IFN)

  1. Screening of CMV encoded genes inhibiting the induction of IFN
  2. Analysis of IFN receptor signaling inhibition by MCMV in vivo 
  3. Identification of HCMV-encoded antagonists of IFN signaling 
  4. Gene signatures in HCMV-stimulated primary human pDC 
  5. Cellular interactions in HCMV-induced type I IFN responses
  6. Protective mechanisms of MCMV-induced type I IFN

Natural Killer Cells (NK Cells) 

  1. MCMV interaction with NK cell receptors
  2. NK cell immunoevasion in acute and chronic MCMV infection 
  3. Interactions between HCMV induced ligands and NK cell receptors
  4. Loading and Maturation of KIR ligands in HCMV infected cells 

Cytotoxic T-cells (CD8+ T-cells)

  1. CMV modulation of MHC-I presentation
  2. CD8 T cell activation
  3. Effector CD8 mechanisms

Partner

Prof. M.D., Ph.D. Luka Cicin-Sain
Junior Research Group “Immune aging and Chronic Infection”
Helmholtz Centre for Infection Research, Braunschweig, Germany

Prof. Dr. Melanie Brinkmann
Junior Research Group “Viral Immune Modulation”
Helmholtz Centre for Infection Research, Braunschweig, Germany

Prof. Dr. rer. nat. Martin Messerle
Virology Department, Research Group “Cytomegalovirus”
Medical School Hannover, Hannover, Germany

Professor Ulrich Kalinke
“Experimental Infection Research”
TWINCORE Centre for Expertmental and Clinical Infection Research, Hannover

Professor Hartmut Hengel
Institute for Virology
University Hospital Düsseldorf
Heinrich-Heine-University, Düsseldorf, Germany

Dr. Anne Halenius
Institute for Virology
University Hospital Düsseldorf
Heinrich-Heine-University, Düsseldorf, Germany

Professor Stipan Jonjic
Medical Faculty, Department for Histology and Embryology
University of Rijeka, Croatia

Projektleiter

Beteiligte Gruppen

Geldgeber / Förderer

Helmholtz

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